Abstract:High-frequency deep brain stimulation (DBS) represents a major stake for treatment for treatment-resistant depression (TRD). We describe a preliminary trial of DBS of two potential brain targets in chronic TRD: the nucleus accumbens (Acb) and, in the event of failure, the caudate nucleus. Patients were followed for 6 months before surgery (M0). From M1 to M5, they underwent stimulation of the Acb target. PET scans allowed us to track metabolic modifications resulting from this stimulation. The caudate target of nonresponders was stimulated between M5 and M9. Patients then entered an extension phase, in which it was possible to adapt stimulation parameters and treatments. Six patients were included and four were operated on. At M5, none of the patients were either responders or remitters, but we did observe a decrease in Hamilton Depression Rating Scale (HDRS) scores. Three patients were switched to caudate stimulation, but no improvement was observed. During the extension phase, the Acb target was stimulated for all patients, three of whom exhibited a significant response. A decrease in glucose metabolism was observed after Acb stimulation, in the posterior cingulate gyrus, left frontal lobe, superior and medial gyrus, and bilateral cerebellum. An increase in metabolism was observed in the bilateral frontal lobe (superior gyrus), left frontal lobe (medial gyrus), and right limbic lobe (anterior cingulate gyrus). The results of this trial suggest that Acb is a more promising target than the caudate. NCT01569711.

Abstract:The so-called obsessive-compulsive spectrum disorder (OCD spectrum) is represented by a large variety of clinical entities. There are in general obsessive-compulsive disorder, trichotillomania or Gilles de la Tourette disease among the impulse control disorders, body dysmorphic disorder and hypochondriasis among the somatoform disorders. Updated overview of the OCD spectrum through a bipolar configuration with the impulsion-compulsion (I-C) spectrum, characterized by a failure to resist and control intrusive thoughts associated with repetitive behaviors that seem to be uncontrollable or require considerable efforts to suppress their execution. There are several disrupted processes in the I-C spectrum, including cognitive control, flexibility and behavioural inhibition. All these psychiatric affections demonstrated to share apparent similarities regarding clinical symptomatology, demographic considerations, comorbidity and course pattern, and responses to the serotonine reuptake inhibitors and cognitive behavioural therapy. The concept of I-C spectrum pleads for less categorical and more dimensional approach that seems to be consistently adapted to clinical, genetic, pathophysiology and therapeutic realities.

Abstract:BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with visuospatial working memory deficits. Intolerance of uncertainty is thought to be a core component of OCD symptoms. Recent findings argue for a possible relationship between abilities in visuospatial memory and uncertainty. However, this relationship remains unclear in both OCD patients and healthy subjects. To address this issue, we measured performance in visuospatial working memory and the propensity to express uncertainty during decision making. We assessed their relationship and the temporal direction of this relationship in both OCD patients and healthy subjects. METHOD: Baseline abilities in visuospatial working memory were measured with the Corsi block-tapping test. A delayed matching-to-sample task was used to identify explicit situations of certainty, uncertainty and ignorance and to assess continuous performance in visuospatial working memory. Behavioural variables were recorded over 360 consecutive trials in both groups. RESULTS: Baseline scores of visuospatial working memory did not predict the number of uncertain situations in OCD patients whereas they did in healthy subjects. Uncertain trials led to reduced abilities in visuospatial working memory to 65% of usual performance in OCD patients whereas they remained stable in healthy subjects. CONCLUSIONS: The present findings show an opposite temporal direction in the relationship between abilities in working memory and uncertainty in OCD patients and healthy subjects. Poor working memory performance contributes to the propensity to feel uncertainty in healthy subjects whereas uncertainty contributes to decreased continuous performance in working memory in OCD patients.

Abstract:BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe anxiety disorder whose symptoms include re-experiencing, avoidance, and hyperarousal after a particularly intense event. In view of the aging of the population, increased clinical knowledge is required for better understanding of PTSD in the elderly. Extending previous research in this field in adults and children, the aim of our study was to assess the utility of peri-traumatic dissociation and distress as a predictor of PTSD in the elderly. METHODS: A prospective longitudinal study was conducted in a consecutive cohort of subjects aged 65 years and over admitted to emergency departments after a physical assault or a road traffic accident. Peri-traumatic responses of distress and of dissociation were measured. One, 6, and 12 months after trauma exposure, PTSD symptoms and diagnosis were assessed using both a dimensional and a semistructured interview. RESULTS: Thirty-nine male and female participants with an average age of 72.4 years were recruited. Mixed model regression analyses did not detect a significant effect of age, sex, nor time. Significant associations were detected between peri-traumatic distress and the self-report PTSD Checklist (p = 0.008), as well as the Clinician-administered PTSD scale (p = 0.03). No association was detected between peri-traumatic dissociation and PTSD. CONCLUSIONS: Peri-traumatic distress predicts PTSD symptoms and diagnosis in the elderly, thereby suggesting its systematic evaluation at the emergency department would be a worthwhile thing to do.

Abstract:BACKGROUND: Compulsive checking behaviors are common in obsessive-compulsive disorder (OCD). Several authors have suggested that these checking rituals could be related to memory deficits. Our aim was to test whether patients with OCD show working memory impairment in relation to their checking behavior. METHODS: We evaluated the verbal and visuospatial components of patients' and controls' working memory using the reading span and backward location span tests. Checking behaviors were measured by recording participants' eye movements during an image comparison task using a non-invasive, infra-red TOBII 1750 eyetracker. Participants were seated, head-free, in a natural position in front of the eyetracker screen where the images were displayed. RESULTS: Patients with OCD made more gaze moves to compare images than controls. Both patients' working memory spans were reduced, and the patients' deficit in the comparison task was negatively related to their working memory spans. CONCLUSIONS: This work demonstrates that checking behavior in OCD is linked to a general reduction of the patients' verbal and visuospatial working memory span.

Abstract:INTRODUCTION: Behavioral adaptation generally follows the contextual changes arising from the consequences (rewards and punishments) of an action. According to the reciprocal determinism model, there is a mutual influence between external context, cognitive processes and behavior. The maladaptive behaviors observed in obsessive-compulsive disorder (OCD) have been hypothesized to result from the disruption of the interactions between these three entities. For this, we assessed the influence of error signals and checking behavior on prefrontal cortical functions during decision-making in 14 OCD patients and 14 matched healthy participants. METHODS: We used a behavioral task designed to elicit intolerance of uncertainty (IU) followed by the free expression of checking behaviors, which was coupled with functional magnetic resonance imaging. RESULTS: At the behavioral level, IU intensity was correlated to the number of checking behaviors in both checking OCD patients and healthy controls during decision-making. However, external error signals did not influence checking behaviors in OCD patients, whereas they appeared to trigger checking behaviors in healthy subjects. At the neural level, IU intensity was positively correlated with activation in the orbitofrontal cortex (OFC) in both the OCD and control groups. At the region of interest (ROI) level, error signals increased IU-related OFC activations; in contrast, checking behaviors contributed to decreasing these neural activations in the healthy subjects, but no such modulation was observed in the OCD patients. CONCLUSIONS: Our results show that IU-related OFC dysfunctions are not under the influence of the context and the behavioral response in OCD, suggesting that alterations of the dynamic features for this neural network may contribute to the expression of OCD symptoms.

Abstract:Obsessive-compulsive disorder (OCD) is a frequent psychiatric disorder characterized by repetitive intrusive thoughts and severe anxiety, leading to compulsive behaviors. Although medical treatment is effective in most cases, resistance is observed in about 30% of patients. In this context, deep brain stimulation (DBS) of the caudate or subthalamic nuclei has been recently proposed with encouraging results. However, some patients were unimproved or exhibited awkward side effects. Therefore, exploration of new targets for DBS remains critical in OCD. In the latter, functional imaging studies revealed overactivity in the limbic and associative cortico-subcortical loops encompassing the thalamus. However, the role of the thalamus in the genesis of repetitive behaviors and related anxiety is unknown. Here, we tested the hypothesis that pharmacological-induced overactivity of the medial thalamus could give rise to abnormal behaviors close to that observed in OCD. We modulated the ventral anterior (VA) and medial dorsal (MD) nuclei activity by in situ bicuculline (GABA(A) antagonist) microinjections in subhuman primates and assessed their pharmacological-induced behavior. Bicuculline injections within the VA caused significant repetitive and time-consuming motor acts whereas those performed within the MD induced symptoms of dysautonomic dysregulation along with abnormal vocalizations and marked motor hypoactivity. These findings suggest that overactivation of the VA and MD nuclei of the thalamus provokes compulsive-like behaviors and neurovegetative manifestations usually associated with the feeling of anxiety in OCD patients. In further research, this translational approach should allow us to test the effectiveness and side effects of these thalamic nuclei DBS in monkey and perhaps, in a second step, to propose a transfer of this technique to severely disabled OCD patients.

Abstract:BACKGROUND: Behavioral inhibition (BI), a heritable temperament, predisposes one to an increased risk of social phobia. Recent investigations have reported that BI may also be a precursor to anxiety as well as depressive and alcohol-related disorders, which are frequently comorbid with social phobia. In the present study, we explored the relationship between BI and psychiatric disorders in 256 adults with a primary diagnosis of social phobia. METHODS: BI severity was retrospectively assessed with the Retrospective Self-Report of Inhibition (RSRI). The severity of social phobia and the presence of comorbid diagnoses were evaluated with the Liebowitz Social Anxiety Scale (LSAS) and the Mini-International Neuropsychiatric Interview, respectively. RESULTS: The RSRI score was significantly and positively correlated with both the LSAS score and the occurrence of a major depressive disorder. No significant association was found with other anxiety and substance-related disorders. LIMITATION: The assessment of BI was retrospective and self-reported. CONCLUSION: A childhood history of BI was associated with an increased risk of depressive comorbidity in social phobia.

Abstract:BACKGROUND: The aim of this study was to investigate the relationship between the levels of insight and checking-related uncertainty in patients with obsessive-compulsive disorder (OCD). SAMPLING AND METHODS: Twenty OCD patients with checking compulsions and without current comorbidity were recruited. We used an experimental paradigm that gave subjects the opportunity to check during a decision-making task, thereby allowing for the calculation of a response time index (RTI) as the 'uncertainty cost' during decision-making. The level of insight was assessed with the Brown Assessment of Beliefs Scale (BABS). RESULTS: Regression analyses indicated a significant positive correlation between RTI and BABS scores (r = 0.49). CONCLUSIONS: The level of insight is related to cognitive characteristics underlying OCD symptoms, in particular, checking-related uncertainty in checking OCD patients. STUDY LIMITATIONS: The absence of a comparison group and the low number of included patients are the main limitations of the present study.